ALBERT

Description: The association of genetic variation with disease and drug response, and improvements in nucleic acid technologies, have given great optimism for the impact of 'genomic medicine'. However, the formidable size of the diploid human genome, approximately 6 gigabases, has prevented the routine application of sequencing methods to deciphering complete individual human genomes. To realize the full potential of genomics for human health, this limitation must be overcome. Here we report the DNA sequence of a diploid genome of a single individual, James D. Watson, sequenced to 7.4-fold redundancy in two months using massively parallel sequencing in picolitre-size reaction vessels. This sequence was completed in two months at approximately one-hundredth of the cost of traditional capillary electrophoresis methods. Comparison of the sequence to the reference genome led to the identification of 3.3 million single nucleotide polymorphisms, of which 10,654 cause amino-acid substitution within the coding sequence. In addition, we accurately identified small-scale (2-40,000 base pair (bp)) insertion and deletion polymorphism as well as copy number variation resulting in the large-scale gain and loss of chromosomal segments ranging from 26,000 to 1.5 million base pairs. Overall, these results agree well with recent results of sequencing of a single individual by traditional methods. However, in addition to being faster and significantly less expensive, this sequencing technology avoids the arbitrary loss of genomic sequences inherent in random shotgun sequencing by bacterial cloning because it amplifies DNA in a cell-free system. As a result, we further demonstrate the acquisition of novel human sequence, including novel genes not previously identified by traditional genomic sequencing. This is the first genome sequenced by next-generation technologies. Therefore it is a pilot for the future challenges of 'personalized genome sequencing'.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wheeler, David A -- Srinivasan, Maithreyan -- Egholm, Michael -- Shen, Yufeng -- Chen, Lei -- McGuire, Amy -- He, Wen -- Chen, Yi-Ju -- Makhijani, Vinod -- Roth, G Thomas -- Gomes, Xavier -- Tartaro, Karrie -- Niazi, Faheem -- Turcotte, Cynthia L -- Irzyk, Gerard P -- Lupski, James R -- Chinault, Craig -- Song, Xing-zhi -- Liu, Yue -- Yuan, Ye -- Nazareth, Lynne -- Qin, Xiang -- Muzny, Donna M -- Margulies, Marcel -- Weinstock, George M -- Gibbs, Richard A -- Rothberg, Jonathan M -- U54 HG003273/HG/NHGRI NIH HHS/ -- England -- Nature. 2008 Apr 17;452(7189):872-6. doi: 10.1038/nature06884.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Human Genome Sequencing Center, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18421352" target="_blank"〉PubMed〈/a〉

Description: Determining the genetic basis of cancer requires comprehensive analyses of large collections of histopathologically well-classified primary tumours. Here we report the results of a collaborative study to discover somatic mutations in 188 human lung adenocarcinomas. DNA sequencing of 623 genes with known or potential relationships to cancer revealed more than 1,000 somatic mutations across the samples. Our analysis identified 26 genes that are mutated at significantly high frequencies and thus are probably involved in carcinogenesis. The frequently mutated genes include tyrosine kinases, among them the EGFR homologue ERBB4; multiple ephrin receptor genes, notably EPHA3; vascular endothelial growth factor receptor KDR; and NTRK genes. These data provide evidence of somatic mutations in primary lung adenocarcinoma for several tumour suppressor genes involved in other cancers--including NF1, APC, RB1 and ATM--and for sequence changes in PTPRD as well as the frequently deleted gene LRP1B. The observed mutational profiles correlate with clinical features, smoking status and DNA repair defects. These results are reinforced by data integration including single nucleotide polymorphism array and gene expression array. Our findings shed further light on several important signalling pathways involved in lung adenocarcinoma, and suggest new molecular targets for treatment.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2694412/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2694412/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ding, Li -- Getz, Gad -- Wheeler, David A -- Mardis, Elaine R -- McLellan, Michael D -- Cibulskis, Kristian -- Sougnez, Carrie -- Greulich, Heidi -- Muzny, Donna M -- Morgan, Margaret B -- Fulton, Lucinda -- Fulton, Robert S -- Zhang, Qunyuan -- Wendl, Michael C -- Lawrence, Michael S -- Larson, David E -- Chen, Ken -- Dooling, David J -- Sabo, Aniko -- Hawes, Alicia C -- Shen, Hua -- Jhangiani, Shalini N -- Lewis, Lora R -- Hall, Otis -- Zhu, Yiming -- Mathew, Tittu -- Ren, Yanru -- Yao, Jiqiang -- Scherer, Steven E -- Clerc, Kerstin -- Metcalf, Ginger A -- Ng, Brian -- Milosavljevic, Aleksandar -- Gonzalez-Garay, Manuel L -- Osborne, John R -- Meyer, Rick -- Shi, Xiaoqi -- Tang, Yuzhu -- Koboldt, Daniel C -- Lin, Ling -- Abbott, Rachel -- Miner, Tracie L -- Pohl, Craig -- Fewell, Ginger -- Haipek, Carrie -- Schmidt, Heather -- Dunford-Shore, Brian H -- Kraja, Aldi -- Crosby, Seth D -- Sawyer, Christopher S -- Vickery, Tammi -- Sander, Sacha -- Robinson, Jody -- Winckler, Wendy -- Baldwin, Jennifer -- Chirieac, Lucian R -- Dutt, Amit -- Fennell, Tim -- Hanna, Megan -- Johnson, Bruce E -- Onofrio, Robert C -- Thomas, Roman K -- Tonon, Giovanni -- Weir, Barbara A -- Zhao, Xiaojun -- Ziaugra, Liuda -- Zody, Michael C -- Giordano, Thomas -- Orringer, Mark B -- Roth, Jack A -- Spitz, Margaret R -- Wistuba, Ignacio I -- Ozenberger, Bradley -- Good, Peter J -- Chang, Andrew C -- Beer, David G -- Watson, Mark A -- Ladanyi, Marc -- Broderick, Stephen -- Yoshizawa, Akihiko -- Travis, William D -- Pao, William -- Province, Michael A -- Weinstock, George M -- Varmus, Harold E -- Gabriel, Stacey B -- Lander, Eric S -- Gibbs, Richard A -- Meyerson, Matthew -- Wilson, Richard K -- P50 CA070907/CA/NCI NIH HHS/ -- R01 CA154365/CA/NCI NIH HHS/ -- U19 CA084953/CA/NCI NIH HHS/ -- U19 CA084953-050003/CA/NCI NIH HHS/ -- U54 HG003067/HG/NHGRI NIH HHS/ -- U54 HG003067-04/HG/NHGRI NIH HHS/ -- U54 HG003273/HG/NHGRI NIH HHS/ -- England -- Nature. 2008 Oct 23;455(7216):1069-75. doi: 10.1038/nature07423.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Genome Center at Washington University, Department of Genetics, Washington University School of Medicine, St Louis, Missouri 63108, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18948947" target="_blank"〉PubMed〈/a〉

Description: The International Cancer Genome Consortium (ICGC) was launched to coordinate large-scale cancer genome studies in tumours from 50 different cancer types and/or subtypes that are of clinical and societal importance across the globe. Systematic studies of more than 25,000 cancer genomes at the genomic, epigenomic and transcriptomic levels will reveal the repertoire of oncogenic mutations, uncover traces of the mutagenic influences, define clinically relevant subtypes for prognosis and therapeutic management, and enable the development of new cancer therapies.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2902243/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2902243/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉International Cancer Genome Consortium -- Hudson, Thomas J -- Anderson, Warwick -- Artez, Axel -- Barker, Anna D -- Bell, Cindy -- Bernabe, Rosa R -- Bhan, M K -- Calvo, Fabien -- Eerola, Iiro -- Gerhard, Daniela S -- Guttmacher, Alan -- Guyer, Mark -- Hemsley, Fiona M -- Jennings, Jennifer L -- Kerr, David -- Klatt, Peter -- Kolar, Patrik -- Kusada, Jun -- Lane, David P -- Laplace, Frank -- Youyong, Lu -- Nettekoven, Gerd -- Ozenberger, Brad -- Peterson, Jane -- Rao, T S -- Remacle, Jacques -- Schafer, Alan J -- Shibata, Tatsuhiro -- Stratton, Michael R -- Vockley, Joseph G -- Watanabe, Koichi -- Yang, Huanming -- Yuen, Matthew M F -- Knoppers, Bartha M -- Bobrow, Martin -- Cambon-Thomsen, Anne -- Dressler, Lynn G -- Dyke, Stephanie O M -- Joly, Yann -- Kato, Kazuto -- Kennedy, Karen L -- Nicolas, Pilar -- Parker, Michael J -- Rial-Sebbag, Emmanuelle -- Romeo-Casabona, Carlos M -- Shaw, Kenna M -- Wallace, Susan -- Wiesner, Georgia L -- Zeps, Nikolajs -- Lichter, Peter -- Biankin, Andrew V -- Chabannon, Christian -- Chin, Lynda -- Clement, Bruno -- de Alava, Enrique -- Degos, Francoise -- Ferguson, Martin L -- Geary, Peter -- Hayes, D Neil -- Johns, Amber L -- Kasprzyk, Arek -- Nakagawa, Hidewaki -- Penny, Robert -- Piris, Miguel A -- Sarin, Rajiv -- Scarpa, Aldo -- van de Vijver, Marc -- Futreal, P Andrew -- Aburatani, Hiroyuki -- Bayes, Monica -- Botwell, David D L -- Campbell, Peter J -- Estivill, Xavier -- Grimmond, Sean M -- Gut, Ivo -- Hirst, Martin -- Lopez-Otin, Carlos -- Majumder, Partha -- Marra, Marco -- McPherson, John D -- Ning, Zemin -- Puente, Xose S -- Ruan, Yijun -- Stunnenberg, Hendrik G -- Swerdlow, Harold -- Velculescu, Victor E -- Wilson, Richard K -- Xue, Hong H -- Yang, Liu -- Spellman, Paul T -- Bader, Gary D -- Boutros, Paul C -- Flicek, Paul -- Getz, Gad -- Guigo, Roderic -- Guo, Guangwu -- Haussler, David -- Heath, Simon -- Hubbard, Tim J -- Jiang, Tao -- Jones, Steven M -- Li, Qibin -- Lopez-Bigas, Nuria -- Luo, Ruibang -- Muthuswamy, Lakshmi -- Ouellette, B F Francis -- Pearson, John V -- Quesada, Victor -- Raphael, Benjamin J -- Sander, Chris -- Speed, Terence P -- Stein, Lincoln D -- Stuart, Joshua M -- Teague, Jon W -- Totoki, Yasushi -- Tsunoda, Tatsuhiko -- Valencia, Alfonso -- Wheeler, David A -- Wu, Honglong -- Zhao, Shancen -- Zhou, Guangyu -- Lathrop, Mark -- Thomas, Gilles -- Yoshida, Teruhiko -- Axton, Myles -- Gunter, Chris -- Miller, Linda J -- Zhang, Junjun -- Haider, Syed A -- Wang, Jianxin -- Yung, Christina K -- Cros, Anthony -- Liang, Yong -- Gnaneshan, Saravanamuttu -- Guberman, Jonathan -- Hsu, Jack -- Chalmers, Don R C -- Hasel, Karl W -- Kaan, Terry S H -- Lowrance, William W -- Masui, Tohru -- Rodriguez, Laura Lyman -- Vergely, Catherine -- Bowtell, David D L -- Cloonan, Nicole -- deFazio, Anna -- Eshleman, James R -- Etemadmoghadam, Dariush -- Gardiner, Brooke B -- Kench, James G -- Sutherland, Robert L -- Tempero, Margaret A -- Waddell, Nicola J -- Wilson, Peter J -- Gallinger, Steve -- Tsao, Ming-Sound -- Shaw, Patricia A -- Petersen, Gloria M -- Mukhopadhyay, Debabrata -- DePinho, Ronald A -- Thayer, Sarah -- Shazand, Kamran -- Beck, Timothy -- Sam, Michelle -- Timms, Lee -- Ballin, Vanessa -- Lu, Youyong -- Ji, Jiafu -- Zhang, Xiuqing -- Chen, Feng -- Hu, Xueda -- Yang, Qi -- Tian, Geng -- Zhang, Lianhai -- Xing, Xiaofang -- Li, Xianghong -- Zhu, Zhenggang -- Yu, Yingyan -- Yu, Jun -- Tost, Jorg -- Brennan, Paul -- Holcatova, Ivana -- Zaridze, David -- Brazma, Alvis -- Egevard, Lars -- Prokhortchouk, Egor -- Banks, Rosamonde Elizabeth -- Uhlen, Mathias -- Viksna, Juris -- Ponten, Fredrik -- Skryabin, Konstantin -- Birney, Ewan -- Borg, Ake -- Borresen-Dale, Anne-Lise -- Caldas, Carlos -- Foekens, John A -- Martin, Sancha -- Reis-Filho, Jorge S -- Richardson, Andrea L -- Sotiriou, Christos -- Thoms, Giles -- van't Veer, Laura -- Birnbaum, Daniel -- Blanche, Helene -- Boucher, Pascal -- Boyault, Sandrine -- Masson-Jacquemier, Jocelyne D -- Pauporte, Iris -- Pivot, Xavier -- Vincent-Salomon, Anne -- Tabone, Eric -- Theillet, Charles -- Treilleux, Isabelle -- Bioulac-Sage, Paulette -- Decaens, Thomas -- Franco, Dominique -- Gut, Marta -- Samuel, Didier -- Zucman-Rossi, Jessica -- Eils, Roland -- Brors, Benedikt -- Korbel, Jan O -- Korshunov, Andrey -- Landgraf, Pablo -- Lehrach, Hans -- Pfister, Stefan -- Radlwimmer, Bernhard -- Reifenberger, Guido -- Taylor, Michael D -- von Kalle, Christof -- Majumder, Partha P -- Pederzoli, Paolo -- Lawlor, Rita A -- Delledonne, Massimo -- Bardelli, Alberto -- Gress, Thomas -- Klimstra, David -- Zamboni, Giuseppe -- Nakamura, Yusuke -- Miyano, Satoru -- Fujimoto, Akihiro -- Campo, Elias -- de Sanjose, Silvia -- Montserrat, Emili -- Gonzalez-Diaz, Marcos -- Jares, Pedro -- Himmelbauer, Heinz -- Bea, Silvia -- Aparicio, Samuel -- Easton, Douglas F -- Collins, Francis S -- Compton, Carolyn C -- Lander, Eric S -- Burke, Wylie -- Green, Anthony R -- Hamilton, Stanley R -- Kallioniemi, Olli P -- Ley, Timothy J -- Liu, Edison T -- Wainwright, Brandon J -- 077198/Wellcome Trust/United Kingdom -- 088340/Wellcome Trust/United Kingdom -- 093867/Wellcome Trust/United Kingdom -- 6613/Cancer Research UK/United Kingdom -- K08 DK071329/DK/NIDDK NIH HHS/ -- K08 DK071329-04/DK/NIDDK NIH HHS/ -- K08 DK071329-05/DK/NIDDK NIH HHS/ -- P01 CA117969/CA/NCI NIH HHS/ -- P01 CA117969-04S1/CA/NCI NIH HHS/ -- P01 CA117969-05/CA/NCI NIH HHS/ -- P50 CA102701/CA/NCI NIH HHS/ -- P50 CA102701-08/CA/NCI NIH HHS/ -- P50 CA127003/CA/NCI NIH HHS/ -- P50 CA127003-04/CA/NCI NIH HHS/ -- P50 CA127003-05/CA/NCI NIH HHS/ -- R01 HG001806-02/HG/NHGRI NIH HHS/ -- England -- Nature. 2010 Apr 15;464(7291):993-8. doi: 10.1038/nature08987.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20393554" target="_blank"〉PubMed〈/a〉

Description: Drosophila males modulate the interpulse intervals produced during their courtship songs. These song cycles, which are altered by mutations in the clock gene period, exhibit a species-specific variation that facilitates mating. We have used chimeric period gene constructs from Drosophila melanogaster and Drosophila simulans in germline transformation experiments to map the genetic control of their song rhythm difference to a small segment of the amino acid encoding information within this gene.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wheeler, D A -- Kyriacou, C P -- Greenacre, M L -- Yu, Q -- Rutila, J E -- Rosbash, M -- Hall, J C -- GM-21473/GM/NIGMS NIH HHS/ -- GM-33205/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1991 Mar 1;251(4997):1082-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, Brandeis University, Waltham, MA 02254.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1900131" target="_blank"〉PubMed〈/a〉

Description: The rhesus macaque (Macaca mulatta) is an abundant primate species that diverged from the ancestors of Homo sapiens about 25 million years ago. Because they are genetically and physiologically similar to humans, rhesus monkeys are the most widely used nonhuman primate in basic and applied biomedical research. We determined the genome sequence of an Indian-origin Macaca mulatta female and compared the data with chimpanzees and humans to reveal the structure of ancestral primate genomes and to identify evidence for positive selection and lineage-specific expansions and contractions of gene families. A comparison of sequences from individual animals was used to investigate their underlying genetic diversity. The complete description of the macaque genome blueprint enhances the utility of this animal model for biomedical research and improves our understanding of the basic biology of the species.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rhesus Macaque Genome Sequencing and Analysis Consortium -- Gibbs, Richard A -- Rogers, Jeffrey -- Katze, Michael G -- Bumgarner, Roger -- Weinstock, George M -- Mardis, Elaine R -- Remington, Karin A -- Strausberg, Robert L -- Venter, J Craig -- Wilson, Richard K -- Batzer, Mark A -- Bustamante, Carlos D -- Eichler, Evan E -- Hahn, Matthew W -- Hardison, Ross C -- Makova, Kateryna D -- Miller, Webb -- Milosavljevic, Aleksandar -- Palermo, Robert E -- Siepel, Adam -- Sikela, James M -- Attaway, Tony -- Bell, Stephanie -- Bernard, Kelly E -- Buhay, Christian J -- Chandrabose, Mimi N -- Dao, Marvin -- Davis, Clay -- Delehaunty, Kimberly D -- Ding, Yan -- Dinh, Huyen H -- Dugan-Rocha, Shannon -- Fulton, Lucinda A -- Gabisi, Ramatu Ayiesha -- Garner, Toni T -- Godfrey, Jennifer -- Hawes, Alicia C -- Hernandez, Judith -- Hines, Sandra -- Holder, Michael -- Hume, Jennifer -- Jhangiani, Shalini N -- Joshi, Vandita -- Khan, Ziad Mohid -- Kirkness, Ewen F -- Cree, Andrew -- Fowler, R Gerald -- Lee, Sandra -- Lewis, Lora R -- Li, Zhangwan -- Liu, Yih-Shin -- Moore, Stephanie M -- Muzny, Donna -- Nazareth, Lynne V -- Ngo, Dinh Ngoc -- Okwuonu, Geoffrey O -- Pai, Grace -- Parker, David -- Paul, Heidie A -- Pfannkoch, Cynthia -- Pohl, Craig S -- Rogers, Yu-Hui -- Ruiz, San Juana -- Sabo, Aniko -- Santibanez, Jireh -- Schneider, Brian W -- Smith, Scott M -- Sodergren, Erica -- Svatek, Amanda F -- Utterback, Teresa R -- Vattathil, Selina -- Warren, Wesley -- White, Courtney Sherell -- Chinwalla, Asif T -- Feng, Yucheng -- Halpern, Aaron L -- Hillier, Ladeana W -- Huang, Xiaoqiu -- Minx, Pat -- Nelson, Joanne O -- Pepin, Kymberlie H -- Qin, Xiang -- Sutton, Granger G -- Venter, Eli -- Walenz, Brian P -- Wallis, John W -- Worley, Kim C -- Yang, Shiaw-Pyng -- Jones, Steven M -- Marra, Marco A -- Rocchi, Mariano -- Schein, Jacqueline E -- Baertsch, Robert -- Clarke, Laura -- Csuros, Miklos -- Glasscock, Jarret -- Harris, R Alan -- Havlak, Paul -- Jackson, Andrew R -- Jiang, Huaiyang -- Liu, Yue -- Messina, David N -- Shen, Yufeng -- Song, Henry Xing-Zhi -- Wylie, Todd -- Zhang, Lan -- Birney, Ewan -- Han, Kyudong -- Konkel, Miriam K -- Lee, Jungnam -- Smit, Arian F A -- Ullmer, Brygg -- Wang, Hui -- Xing, Jinchuan -- Burhans, Richard -- Cheng, Ze -- Karro, John E -- Ma, Jian -- Raney, Brian -- She, Xinwei -- Cox, Michael J -- Demuth, Jeffery P -- Dumas, Laura J -- Han, Sang-Gook -- Hopkins, Janet -- Karimpour-Fard, Anis -- Kim, Young H -- Pollack, Jonathan R -- Vinar, Tomas -- Addo-Quaye, Charles -- Degenhardt, Jeremiah -- Denby, Alexandra -- Hubisz, Melissa J -- Indap, Amit -- Kosiol, Carolin -- Lahn, Bruce T -- Lawson, Heather A -- Marklein, Alison -- Nielsen, Rasmus -- Vallender, Eric J -- Clark, Andrew G -- Ferguson, Betsy -- Hernandez, Ryan D -- Hirani, Kashif -- Kehrer-Sawatzki, Hildegard -- Kolb, Jessica -- Patil, Shobha -- Pu, Ling-Ling -- Ren, Yanru -- Smith, David Glenn -- Wheeler, David A -- Schenck, Ian -- Ball, Edward V -- Chen, Rui -- Cooper, David N -- Giardine, Belinda -- Hsu, Fan -- Kent, W James -- Lesk, Arthur -- Nelson, David L -- O'brien, William E -- Prufer, Kay -- Stenson, Peter D -- Wallace, James C -- Ke, Hui -- Liu, Xiao-Ming -- Wang, Peng -- Xiang, Andy Peng -- Yang, Fan -- Barber, Galt P -- Haussler, David -- Karolchik, Donna -- Kern, Andy D -- Kuhn, Robert M -- Smith, Kayla E -- Zwieg, Ann S -- 062023/Wellcome Trust/United Kingdom -- R01 HG002939/HG/NHGRI NIH HHS/ -- U54 HG003068/HG/NHGRI NIH HHS/ -- U54 HG003079/HG/NHGRI NIH HHS/ -- U54 HG003273/HG/NHGRI NIH HHS/ -- New York, N.Y. -- Science. 2007 Apr 13;316(5822):222-34.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA. agibbs@bcm.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17431167" target="_blank"〉PubMed〈/a〉

Description: The imprints of domestication and breed development on the genomes of livestock likely differ from those of companion animals. A deep draft sequence assembly of shotgun reads from a single Hereford female and comparative sequences sampled from six additional breeds were used to develop probes to interrogate 37,470 single-nucleotide polymorphisms (SNPs) in 497 cattle from 19 geographically and biologically diverse breeds. These data show that cattle have undergone a rapid recent decrease in effective population size from a very large ancestral population, possibly due to bottlenecks associated with domestication, selection, and breed formation. Domestication and artificial selection appear to have left detectable signatures of selection within the cattle genome, yet the current levels of diversity within breeds are at least as great as exists within humans.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2735092/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2735092/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bovine HapMap Consortium -- Gibbs, Richard A -- Taylor, Jeremy F -- Van Tassell, Curtis P -- Barendse, William -- Eversole, Kellye A -- Gill, Clare A -- Green, Ronnie D -- Hamernik, Debora L -- Kappes, Steven M -- Lien, Sigbjorn -- Matukumalli, Lakshmi K -- McEwan, John C -- Nazareth, Lynne V -- Schnabel, Robert D -- Weinstock, George M -- Wheeler, David A -- Ajmone-Marsan, Paolo -- Boettcher, Paul J -- Caetano, Alexandre R -- Garcia, Jose Fernando -- Hanotte, Olivier -- Mariani, Paola -- Skow, Loren C -- Sonstegard, Tad S -- Williams, John L -- Diallo, Boubacar -- Hailemariam, Lemecha -- Martinez, Mario L -- Morris, Chris A -- Silva, Luiz O C -- Spelman, Richard J -- Mulatu, Woudyalew -- Zhao, Keyan -- Abbey, Colette A -- Agaba, Morris -- Araujo, Flabio R -- Bunch, Rowan J -- Burton, James -- Gorni, Chiara -- Olivier, Hanotte -- Harrison, Blair E -- Luff, Bill -- Machado, Marco A -- Mwakaya, Joel -- Plastow, Graham -- Sim, Warren -- Smith, Timothy -- Thomas, Merle B -- Valentini, Alessio -- Williams, Paul -- Womack, James -- Woolliams, John A -- Liu, Yue -- Qin, Xiang -- Worley, Kim C -- Gao, Chuan -- Jiang, Huaiyang -- Moore, Stephen S -- Ren, Yanru -- Song, Xing-Zhi -- Bustamante, Carlos D -- Hernandez, Ryan D -- Muzny, Donna M -- Patil, Shobha -- San Lucas, Anthony -- Fu, Qing -- Kent, Matthew P -- Vega, Richard -- Matukumalli, Aruna -- McWilliam, Sean -- Sclep, Gert -- Bryc, Katarzyna -- Choi, Jungwoo -- Gao, Hong -- Grefenstette, John J -- Murdoch, Brenda -- Stella, Alessandra -- Villa-Angulo, Rafael -- Wright, Mark -- Aerts, Jan -- Jann, Oliver -- Negrini, Riccardo -- Goddard, Mike E -- Hayes, Ben J -- Bradley, Daniel G -- Barbosa da Silva, Marcos -- Lau, Lilian P L -- Liu, George E -- Lynn, David J -- Panzitta, Francesca -- Dodds, Ken G -- R01 GM083606/GM/NIGMS NIH HHS/ -- R01 GM083606-02/GM/NIGMS NIH HHS/ -- U54 HG003273/HG/NHGRI NIH HHS/ -- New York, N.Y. -- Science. 2009 Apr 24;324(5926):528-32. doi: 10.1126/science.1167936.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19390050" target="_blank"〉PubMed〈/a〉

Description: Infectious and inflammatory diseases have repeatedly shown strong genetic associations within the major histocompatibility complex (MHC); however, the basis for these associations remains elusive. To define host genetic effects on the outcome of a chronic viral infection, we performed genome-wide association analysis in a multiethnic cohort of HIV-1 controllers and progressors, and we analyzed the effects of individual amino acids within the classical human leukocyte antigen (HLA) proteins. We identified 〉300 genome-wide significant single-nucleotide polymorphisms (SNPs) within the MHC and none elsewhere. Specific amino acids in the HLA-B peptide binding groove, as well as an independent HLA-C effect, explain the SNP associations and reconcile both protective and risk HLA alleles. These results implicate the nature of the HLA-viral peptide interaction as the major factor modulating durable control of HIV infection.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3235490/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3235490/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉International HIV Controllers Study -- Pereyra, Florencia -- Jia, Xiaoming -- McLaren, Paul J -- Telenti, Amalio -- de Bakker, Paul I W -- Walker, Bruce D -- Ripke, Stephan -- Brumme, Chanson J -- Pulit, Sara L -- Carrington, Mary -- Kadie, Carl M -- Carlson, Jonathan M -- Heckerman, David -- Graham, Robert R -- Plenge, Robert M -- Deeks, Steven G -- Gianniny, Lauren -- Crawford, Gabriel -- Sullivan, Jordan -- Gonzalez, Elena -- Davies, Leela -- Camargo, Amy -- Moore, Jamie M -- Beattie, Nicole -- Gupta, Supriya -- Crenshaw, Andrew -- Burtt, Noel P -- Guiducci, Candace -- Gupta, Namrata -- Gao, Xiaojiang -- Qi, Ying -- Yuki, Yuko -- Piechocka-Trocha, Alicja -- Cutrell, Emily -- Rosenberg, Rachel -- Moss, Kristin L -- Lemay, Paul -- O'Leary, Jessica -- Schaefer, Todd -- Verma, Pranshu -- Toth, Ildiko -- Block, Brian -- Baker, Brett -- Rothchild, Alissa -- Lian, Jeffrey -- Proudfoot, Jacqueline -- Alvino, Donna Marie L -- Vine, Seanna -- Addo, Marylyn M -- Allen, Todd M -- Altfeld, Marcus -- Henn, Matthew R -- Le Gall, Sylvie -- Streeck, Hendrik -- Haas, David W -- Kuritzkes, Daniel R -- Robbins, Gregory K -- Shafer, Robert W -- Gulick, Roy M -- Shikuma, Cecilia M -- Haubrich, Richard -- Riddler, Sharon -- Sax, Paul E -- Daar, Eric S -- Ribaudo, Heather J -- Agan, Brian -- Agarwal, Shanu -- Ahern, Richard L -- Allen, Brady L -- Altidor, Sherly -- Altschuler, Eric L -- Ambardar, Sujata -- Anastos, Kathryn -- Anderson, Ben -- Anderson, Val -- Andrady, Ushan -- Antoniskis, Diana -- Bangsberg, David -- Barbaro, Daniel -- Barrie, William -- Bartczak, J -- Barton, Simon -- Basden, Patricia -- Basgoz, Nesli -- Bazner, Suzane -- Bellos, Nicholaos C -- Benson, Anne M -- Berger, Judith -- Bernard, Nicole F -- Bernard, Annette M -- Birch, Christopher -- Bodner, Stanley J -- Bolan, Robert K -- Boudreaux, Emilie T -- Bradley, Meg -- Braun, James F -- Brndjar, Jon E -- Brown, Stephen J -- Brown, Katherine -- Brown, Sheldon T -- Burack, Jedidiah -- Bush, Larry M -- Cafaro, Virginia -- Campbell, Omobolaji -- Campbell, John -- Carlson, Robert H -- Carmichael, J Kevin -- Casey, Kathleen K -- Cavacuiti, Chris -- Celestin, Gregory -- Chambers, Steven T -- Chez, Nancy -- Chirch, Lisa M -- Cimoch, Paul J -- Cohen, Daniel -- Cohn, Lillian E -- Conway, Brian -- Cooper, David A -- Cornelson, Brian -- Cox, David T -- Cristofano, Michael V -- Cuchural, George Jr -- Czartoski, Julie L -- Dahman, Joseph M -- Daly, Jennifer S -- Davis, Benjamin T -- Davis, Kristine -- Davod, Sheila M -- DeJesus, Edwin -- Dietz, Craig A -- Dunham, Eleanor -- Dunn, Michael E -- Ellerin, Todd B -- Eron, Joseph J -- Fangman, John J W -- Farel, Claire E -- Ferlazzo, Helen -- Fidler, Sarah -- Fleenor-Ford, Anita -- Frankel, Renee -- Freedberg, Kenneth A -- French, Neel K -- Fuchs, Jonathan D -- Fuller, Jon D -- Gaberman, Jonna -- Gallant, Joel E -- Gandhi, Rajesh T -- Garcia, Efrain -- Garmon, Donald -- Gathe, Joseph C Jr -- Gaultier, Cyril R -- Gebre, Wondwoosen -- Gilman, Frank D -- Gilson, Ian -- Goepfert, Paul A -- Gottlieb, Michael S -- Goulston, Claudia -- Groger, Richard K -- Gurley, T Douglas -- Haber, Stuart -- Hardwicke, Robin -- Hardy, W David -- Harrigan, P Richard -- Hawkins, Trevor N -- Heath, Sonya -- Hecht, Frederick M -- Henry, W Keith -- Hladek, Melissa -- Hoffman, Robert P -- Horton, James M -- Hsu, Ricky K -- Huhn, Gregory D -- Hunt, Peter -- Hupert, Mark J -- Illeman, Mark L -- Jaeger, Hans -- Jellinger, Robert M -- John, Mina -- Johnson, Jennifer A -- Johnson, Kristin L -- Johnson, Heather -- Johnson, Kay -- Joly, Jennifer -- Jordan, Wilbert C -- Kauffman, Carol A -- Khanlou, Homayoon -- Killian, Robert K -- Kim, Arthur Y -- Kim, David D -- Kinder, Clifford A -- Kirchner, Jeffrey T -- Kogelman, Laura -- Kojic, Erna Milunka -- Korthuis, P Todd -- Kurisu, Wayne -- Kwon, Douglas S -- LaMar, Melissa -- Lampiris, Harry -- Lanzafame, Massimiliano -- Lederman, Michael M -- Lee, David M -- Lee, Jean M L -- Lee, Marah J -- Lee, Edward T Y -- Lemoine, Janice -- Levy, Jay A -- Llibre, Josep M -- Liguori, Michael A -- Little, Susan J -- Liu, Anne Y -- Lopez, Alvaro J -- Loutfy, Mono R -- Loy, Dawn -- Mohammed, Debbie Y -- Man, Alan -- Mansour, Michael K -- Marconi, Vincent C -- Markowitz, Martin -- Marques, Rui -- Martin, Jeffrey N -- Martin, Harold L Jr -- Mayer, Kenneth Hugh -- McElrath, M Juliana -- McGhee, Theresa A -- McGovern, Barbara H -- McGowan, Katherine -- McIntyre, Dawn -- Mcleod, Gavin X -- Menezes, Prema -- Mesa, Greg -- Metroka, Craig E -- Meyer-Olson, Dirk -- Miller, Andy O -- Montgomery, Kate -- Mounzer, Karam C -- Nagami, Ellen H -- Nagin, Iris -- Nahass, Ronald G -- Nelson, Margret O -- Nielsen, Craig -- Norene, David L -- O'Connor, David H -- Ojikutu, Bisola O -- Okulicz, Jason -- Oladehin, Olakunle O -- Oldfield, Edward C 3rd -- Olender, Susan A -- Ostrowski, Mario -- Owen, William F Jr -- Pae, Eunice -- Parsonnet, Jeffrey -- Pavlatos, Andrew M -- Perlmutter, Aaron M -- Pierce, Michael N -- Pincus, Jonathan M -- Pisani, Leandro -- Price, Lawrence Jay -- Proia, Laurie -- Prokesch, Richard C -- Pujet, Heather Calderon -- Ramgopal, Moti -- Rathod, Almas -- Rausch, Michael -- Ravishankar, J -- Rhame, Frank S -- Richards, Constance Shamuyarira -- Richman, Douglas D -- Rodes, Berta -- Rodriguez, Milagros -- Rose, Richard C 3rd -- Rosenberg, Eric S -- Rosenthal, Daniel -- Ross, Polly E -- Rubin, David S -- Rumbaugh, Elease -- Saenz, Luis -- Salvaggio, Michelle R -- Sanchez, William C -- Sanjana, Veeraf M -- Santiago, Steven -- Schmidt, Wolfgang -- Schuitemaker, Hanneke -- Sestak, Philip M -- Shalit, Peter -- Shay, William -- Shirvani, Vivian N -- Silebi, Vanessa I -- Sizemore, James M Jr -- Skolnik, Paul R -- Sokol-Anderson, Marcia -- Sosman, James M -- Stabile, Paul -- Stapleton, Jack T -- Starrett, Sheree -- Stein, Francine -- Stellbrink, Hans-Jurgen -- Sterman, F Lisa -- Stone, Valerie E -- Stone, David R -- Tambussi, Giuseppe -- Taplitz, Randy A -- Tedaldi, Ellen M -- Theisen, William -- Torres, Richard -- Tosiello, Lorraine -- Tremblay, Cecile -- Tribble, Marc A -- Trinh, Phuong D -- Tsao, Alice -- Ueda, Peggy -- Vaccaro, Anthony -- Valadas, Emilia -- Vanig, Thanes J -- Vecino, Isabel -- Vega, Vilma M -- Veikley, Wenoah -- Wade, Barbara H -- Walworth, Charles -- Wanidworanun, Chingchai -- Ward, Douglas J -- Warner, Daniel A -- Weber, Robert D -- Webster, Duncan -- Weis, Steve -- Wheeler, David A -- White, David J -- Wilkins, Ed -- Winston, Alan -- Wlodaver, Clifford G -- van't Wout, Angelique -- Wright, David P -- Yang, Otto O -- Yurdin, David L -- Zabukovic, Brandon W -- Zachary, Kimon C -- Zeeman, Beth -- Zhao, Meng -- AI030914/AI/NIAID NIH HHS/ -- AI068636/AI/NIAID NIH HHS/ -- AI069415/AI/NIAID NIH HHS/ -- AI069419/AI/NIAID NIH HHS/ -- AI069423/AI/NIAID NIH HHS/ -- AI069424/AI/NIAID NIH HHS/ -- AI069428/AI/NIAID NIH HHS/ -- AI069432/AI/NIAID NIH HHS/ -- AI069434/AI/NIAID NIH HHS/ -- AI069450/AI/NIAID NIH HHS/ -- AI069452/AI/NIAID NIH HHS/ -- AI069465/AI/NIAID NIH HHS/ -- AI069471/AI/NIAID NIH HHS/ -- AI069472/AI/NIAID NIH HHS/ -- AI069474/AI/NIAID NIH HHS/ -- AI069477/AI/NIAID NIH HHS/ -- AI069484/AI/NIAID NIH HHS/ -- AI069495/AI/NIAID NIH HHS/ -- AI069501/AI/NIAID NIH HHS/ -- AI069502/AI/NIAID NIH HHS/ -- AI069511/AI/NIAID NIH HHS/ -- AI069513/AI/NIAID NIH HHS/ -- AI069532/AI/NIAID NIH HHS/ -- AI069556/AI/NIAID NIH HHS/ -- AI077505/AI/NIAID NIH HHS/ -- AI087145/AI/NIAID NIH HHS/ -- AI25859/AI/NIAID NIH HHS/ -- AI27661/AI/NIAID NIH HHS/ -- AI28568/AI/NIAID NIH HHS/ -- AI30914/AI/NIAID NIH HHS/ -- AI34835/AI/NIAID NIH HHS/ -- AI34853/AI/NIAID NIH HHS/ -- AI38844/AI/NIAID NIH HHS/ -- AI46370/AI/NIAID NIH HHS/ -- AI68634/AI/NIAID NIH HHS/ -- AI69467/AI/NIAID NIH HHS/ -- AL32782/PHS HHS/ -- HHSN261200800001E/PHS HHS/ -- K23 DA019809/DA/NIDA NIH HHS/ -- K24 AI051966/AI/NIAID NIH HHS/ -- K24 AI064086/AI/NIAID NIH HHS/ -- K24 AI064086-05/AI/NIAID NIH HHS/ -- K24 AI069994/AI/NIAID NIH HHS/ -- K24 AI069994-04/AI/NIAID NIH HHS/ -- K24 AI069994-05/AI/NIAID NIH HHS/ -- K24AI069994/AI/NIAID NIH HHS/ -- KL2 RR024977/RR/NCRR NIH HHS/ -- MH071205/MH/NIMH NIH HHS/ -- MH085520/MH/NIMH NIH HHS/ -- P-30 AI27763/AI/NIAID NIH HHS/ -- P-30-AI060354/AI/NIAID NIH HHS/ -- P30 AI027763/AI/NIAID NIH HHS/ -- P30 AI027763-19/AI/NIAID NIH HHS/ -- P30 AI027763-20/AI/NIAID NIH HHS/ -- P30 AI050410/AI/NIAID NIH HHS/ -- P30 AI060354/AI/NIAID NIH HHS/ -- P30 AI060354-08/AI/NIAID NIH HHS/ -- P30 AI060354-09/AI/NIAID NIH HHS/ -- 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AI034835-07/AI/NIAID NIH HHS/ -- U01 AI034835-07S3/AI/NIAID NIH HHS/ -- U01 AI034853/AI/NIAID NIH HHS/ -- U01 AI034853-11/AI/NIAID NIH HHS/ -- U01 AI034853-12/AI/NIAID NIH HHS/ -- U01 AI038844-04/AI/NIAID NIH HHS/ -- U01 AI038844-04S1/AI/NIAID NIH HHS/ -- U01 AI038844-04S2/AI/NIAID NIH HHS/ -- U01 AI038844-04S3/AI/NIAID NIH HHS/ -- U01 AI046370-04/AI/NIAID NIH HHS/ -- U01 AI046370-05/AI/NIAID NIH HHS/ -- U01 AI069419/AI/NIAID NIH HHS/ -- U01 AI069419-05/AI/NIAID NIH HHS/ -- U01 AI069419-06/AI/NIAID NIH HHS/ -- U01 AI069423/AI/NIAID NIH HHS/ -- U01 AI069423-05/AI/NIAID NIH HHS/ -- U01 AI069423-06/AI/NIAID NIH HHS/ -- U01 AI069424/AI/NIAID NIH HHS/ -- U01 AI069424-05/AI/NIAID NIH HHS/ -- U01 AI069424-06/AI/NIAID NIH HHS/ -- U01 AI069428/AI/NIAID NIH HHS/ -- U01 AI069428-05/AI/NIAID NIH HHS/ -- U01 AI069428-06/AI/NIAID NIH HHS/ -- U01 AI069432/AI/NIAID NIH HHS/ -- U01 AI069432-05/AI/NIAID NIH HHS/ -- U01 AI069432-06/AI/NIAID NIH HHS/ -- U01 AI069434/AI/NIAID NIH HHS/ -- U01 AI069434-05/AI/NIAID NIH HHS/ -- U01 AI069434-06/AI/NIAID NIH HHS/ -- U01 AI069450/AI/NIAID NIH HHS/ -- U01 AI069450-05/AI/NIAID NIH HHS/ -- U01 AI069450-06/AI/NIAID NIH HHS/ -- U01 AI069452/AI/NIAID NIH HHS/ -- U01 AI069452-05/AI/NIAID NIH HHS/ -- U01 AI069452-06/AI/NIAID NIH HHS/ -- U01 AI069465/AI/NIAID NIH HHS/ -- U01 AI069465-05/AI/NIAID NIH HHS/ -- U01 AI069465-06/AI/NIAID NIH HHS/ -- U01 AI069467/AI/NIAID NIH HHS/ -- U01 AI069467-05/AI/NIAID NIH HHS/ -- U01 AI069467-06/AI/NIAID NIH HHS/ -- U01 AI069471/AI/NIAID NIH HHS/ -- U01 AI069471-05/AI/NIAID NIH HHS/ -- U01 AI069471-06/AI/NIAID NIH HHS/ -- U01 AI069472/AI/NIAID NIH HHS/ -- U01 AI069472-05/AI/NIAID NIH HHS/ -- U01 AI069472-06/AI/NIAID NIH HHS/ -- U01 AI069474/AI/NIAID NIH HHS/ -- U01 AI069474-05/AI/NIAID NIH HHS/ -- U01 AI069474-06/AI/NIAID NIH HHS/ -- U01 AI069477/AI/NIAID NIH HHS/ -- U01 AI069477-05/AI/NIAID NIH HHS/ -- U01 AI069477-06/AI/NIAID NIH HHS/ -- U01 AI069484/AI/NIAID NIH HHS/ -- U01 AI069484-05/AI/NIAID NIH HHS/ -- U01 AI069484-06/AI/NIAID NIH HHS/ -- U01 AI069495/AI/NIAID NIH HHS/ -- U01 AI069495-05/AI/NIAID NIH HHS/ -- U01 AI069495-06/AI/NIAID NIH HHS/ -- U01 AI069501/AI/NIAID NIH HHS/ -- U01 AI069501-05/AI/NIAID NIH HHS/ -- U01 AI069501-06/AI/NIAID NIH HHS/ -- U01 AI069502/AI/NIAID NIH HHS/ -- U01 AI069502-05/AI/NIAID NIH HHS/ -- U01 AI069502-06/AI/NIAID NIH HHS/ -- U01 AI069511/AI/NIAID NIH HHS/ -- U01 AI069511-05/AI/NIAID NIH HHS/ -- U01 AI069511-06/AI/NIAID NIH HHS/ -- U01 AI069513-05/AI/NIAID NIH HHS/ -- U01 AI069513-06/AI/NIAID NIH HHS/ -- U01 AI069532/AI/NIAID NIH HHS/ -- U01 AI069532-05/AI/NIAID NIH HHS/ -- U01 AI069532-06/AI/NIAID NIH HHS/ -- U01 AI069556-05/AI/NIAID NIH HHS/ -- U01 AI069556-06/AI/NIAID NIH HHS/ -- U01 MH085520/MH/NIMH NIH HHS/ -- U01 MH085520-01/MH/NIMH NIH HHS/ -- UL1 RR024131/RR/NCRR NIH HHS/ -- UL1 RR024131-06/RR/NCRR NIH HHS/ -- UL1 RR024131-07/RR/NCRR NIH HHS/ -- UL1 RR024975/RR/NCRR NIH HHS/ -- UL1 RR024975-04/RR/NCRR NIH HHS/ -- UL1 RR024975-05/RR/NCRR NIH HHS/ -- UM1 AI068634/AI/NIAID NIH HHS/ -- UM1 AI068634-06/AI/NIAID NIH HHS/ -- UM1 AI068634-07/AI/NIAID NIH HHS/ -- UM1 AI068636-06/AI/NIAID NIH HHS/ -- UM1 AI068636-07/AI/NIAID NIH HHS/ -- UM1 AI069477/AI/NIAID NIH HHS/ -- Howard Hughes Medical Institute/ -- Intramural NIH HHS/ -- New York, N.Y. -- Science. 2010 Dec 10;330(6010):1551-7. doi: 10.1126/science.1195271. Epub 2010 Nov 4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology (MIT) and Harvard, Boston, MA, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21051598" target="_blank"〉PubMed〈/a〉

Description: Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide. To explore the genetic origins of this cancer, we used whole-exome sequencing and gene copy number analyses to study 32 primary tumors. Tumors from patients with a history of tobacco use had more mutations than did tumors from patients who did not use tobacco, and tumors that were negative for human papillomavirus (HPV) had more mutations than did HPV-positive tumors. Six of the genes that were mutated in multiple tumors were assessed in up to 88 additional HNSCCs. In addition to previously described mutations in TP53, CDKN2A, PIK3CA, and HRAS, we identified mutations in FBXW7 and NOTCH1. Nearly 40% of the 28 mutations identified in NOTCH1 were predicted to truncate the gene product, suggesting that NOTCH1 may function as a tumor suppressor gene rather than an oncogene in this tumor type.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3162986/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3162986/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Agrawal, Nishant -- Frederick, Mitchell J -- Pickering, Curtis R -- Bettegowda, Chetan -- Chang, Kyle -- Li, Ryan J -- Fakhry, Carole -- Xie, Tong-Xin -- Zhang, Jiexin -- Wang, Jing -- Zhang, Nianxiang -- El-Naggar, Adel K -- Jasser, Samar A -- Weinstein, John N -- Trevino, Lisa -- Drummond, Jennifer A -- Muzny, Donna M -- Wu, Yuanqing -- Wood, Laura D -- Hruban, Ralph H -- Westra, William H -- Koch, Wayne M -- Califano, Joseph A -- Gibbs, Richard A -- Sidransky, David -- Vogelstein, Bert -- Velculescu, Victor E -- Papadopoulos, Nickolas -- Wheeler, David A -- Kinzler, Kenneth W -- Myers, Jeffrey N -- 5P50CA09700708/CA/NCI NIH HHS/ -- CA121113/CA/NCI NIH HHS/ -- CA16672/CA/NCI NIH HHS/ -- CA43460/CA/NCI NIH HHS/ -- CA57345/CA/NCI NIH HHS/ -- CN43302/CN/NCI NIH HHS/ -- N01 CN043302/CN/NCI NIH HHS/ -- P50 CA097007/CA/NCI NIH HHS/ -- P50 CA097007-05/CA/NCI NIH HHS/ -- P50 DE019032/DE/NIDCR NIH HHS/ -- P50 DE019032-07/DE/NIDCR NIH HHS/ -- P50 DE019032-10/DE/NIDCR NIH HHS/ -- P50DE019032/DE/NIDCR NIH HHS/ -- R01 CA121113/CA/NCI NIH HHS/ -- R01 CA121113-01/CA/NCI NIH HHS/ -- R37 CA043460/CA/NCI NIH HHS/ -- R37 CA043460-16/CA/NCI NIH HHS/ -- R37 CA057345/CA/NCI NIH HHS/ -- R37 CA057345-20/CA/NCI NIH HHS/ -- R37 DE012588/DE/NIDCR NIH HHS/ -- R37 DE012588-14/DE/NIDCR NIH HHS/ -- RC2 DE020957/DE/NIDCR NIH HHS/ -- RC2 DE020957-01/DE/NIDCR NIH HHS/ -- RC2 DE020957-02/DE/NIDCR NIH HHS/ -- RC2 DE020958/DE/NIDCR NIH HHS/ -- RC2 DE020958-02/DE/NIDCR NIH HHS/ -- RC2DE020957/DE/NIDCR NIH HHS/ -- RC2DE020958/DE/NIDCR NIH HHS/ -- T32 CA009574/CA/NCI NIH HHS/ -- U54 HG003273/HG/NHGRI NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2011 Aug 26;333(6046):1154-7. doi: 10.1126/science.1206923. Epub 2011 Jul 28.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Baltimore, MD 21287, USA. nagrawal@jhmi.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21798897" target="_blank"〉PubMed〈/a〉

Description: Pancreatic cancer is a highly lethal malignancy with few effective therapies. We performed exome sequencing and copy number analysis to define genomic aberrations in a prospectively accrued clinical cohort (n = 142) of early (stage I and II) sporadic pancreatic ductal adenocarcinoma. Detailed analysis of 99 informative tumours identified substantial heterogeneity with 2,016 non-silent mutations and 1,628 copy-number variations. We define 16 significantly mutated genes, reaffirming known mutations (KRAS, TP53, CDKN2A, SMAD4, MLL3, TGFBR2, ARID1A and SF3B1), and uncover novel mutated genes including additional genes involved in chromatin modification (EPC1 and ARID2), DNA damage repair (ATM) and other mechanisms (ZIM2, MAP2K4, NALCN, SLC16A4 and MAGEA6). Integrative analysis with in vitro functional data and animal models provided supportive evidence for potential roles for these genetic aberrations in carcinogenesis. Pathway-based analysis of recurrently mutated genes recapitulated clustering in core signalling pathways in pancreatic ductal adenocarcinoma, and identified new mutated genes in each pathway. We also identified frequent and diverse somatic aberrations in genes described traditionally as embryonic regulators of axon guidance, particularly SLIT/ROBO signalling, which was also evident in murine Sleeping Beauty transposon-mediated somatic mutagenesis models of pancreatic cancer, providing further supportive evidence for the potential involvement of axon guidance genes in pancreatic carcinogenesis.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3530898/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3530898/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Biankin, Andrew V -- Waddell, Nicola -- Kassahn, Karin S -- Gingras, Marie-Claude -- Muthuswamy, Lakshmi B -- Johns, Amber L -- Miller, David K -- Wilson, Peter J -- Patch, Ann-Marie -- Wu, Jianmin -- Chang, David K -- Cowley, Mark J -- Gardiner, Brooke B -- Song, Sarah -- Harliwong, Ivon -- Idrisoglu, Senel -- Nourse, Craig -- Nourbakhsh, Ehsan -- Manning, Suzanne -- Wani, Shivangi -- Gongora, Milena -- Pajic, Marina -- Scarlett, Christopher J -- Gill, Anthony J -- Pinho, Andreia V -- Rooman, Ilse -- Anderson, Matthew -- Holmes, Oliver -- Leonard, Conrad -- Taylor, Darrin -- Wood, Scott -- Xu, Qinying -- Nones, Katia -- Fink, J Lynn -- Christ, Angelika -- Bruxner, Tim -- Cloonan, Nicole -- Kolle, Gabriel -- Newell, Felicity -- Pinese, Mark -- Mead, R Scott -- Humphris, Jeremy L -- Kaplan, Warren -- Jones, Marc D -- Colvin, Emily K -- Nagrial, Adnan M -- Humphrey, Emily S -- Chou, Angela -- Chin, Venessa T -- Chantrill, Lorraine A -- Mawson, Amanda -- Samra, Jaswinder S -- Kench, James G -- Lovell, Jessica A -- Daly, Roger J -- Merrett, Neil D -- Toon, Christopher -- Epari, Krishna -- Nguyen, Nam Q -- Barbour, Andrew -- Zeps, Nikolajs -- Australian Pancreatic Cancer Genome Initiative -- Kakkar, Nipun -- Zhao, Fengmei -- Wu, Yuan Qing -- Wang, Min -- Muzny, Donna M -- Fisher, William E -- Brunicardi, F Charles -- Hodges, Sally E -- Reid, Jeffrey G -- Drummond, Jennifer -- Chang, Kyle -- Han, Yi -- Lewis, Lora R -- Dinh, Huyen -- Buhay, Christian J -- Beck, Timothy -- Timms, Lee -- Sam, Michelle -- Begley, Kimberly -- Brown, Andrew -- Pai, Deepa -- Panchal, Ami -- Buchner, Nicholas -- De Borja, Richard -- Denroche, Robert E -- Yung, Christina K -- Serra, Stefano -- Onetto, Nicole -- Mukhopadhyay, Debabrata -- Tsao, Ming-Sound -- Shaw, Patricia A -- Petersen, Gloria M -- Gallinger, Steven -- Hruban, Ralph H -- Maitra, Anirban -- Iacobuzio-Donahue, Christine A -- Schulick, Richard D -- Wolfgang, Christopher L -- Morgan, Richard A -- Lawlor, Rita T -- Capelli, Paola -- Corbo, Vincenzo -- Scardoni, Maria -- Tortora, Giampaolo -- Tempero, Margaret A -- Mann, Karen M -- Jenkins, Nancy A -- Perez-Mancera, Pedro A -- Adams, David J -- Largaespada, David A -- Wessels, Lodewyk F A -- Rust, Alistair G -- Stein, Lincoln D -- Tuveson, David A -- Copeland, Neal G -- Musgrove, Elizabeth A -- Scarpa, Aldo -- Eshleman, James R -- Hudson, Thomas J -- Sutherland, Robert L -- Wheeler, David A -- Pearson, John V -- McPherson, John D -- Gibbs, Richard A -- Grimmond, Sean M -- 13031/Cancer Research UK/United Kingdom -- 2P50CA101955/CA/NCI NIH HHS/ -- P01CA134292/CA/NCI NIH HHS/ -- P50 CA101955/CA/NCI NIH HHS/ -- P50 CA102701/CA/NCI NIH HHS/ -- P50CA062924/CA/NCI NIH HHS/ -- R01 CA097075/CA/NCI NIH HHS/ -- R01 CA97075/CA/NCI NIH HHS/ -- U54 HG003273/HG/NHGRI NIH HHS/ -- Cancer Research UK/United Kingdom -- Wellcome Trust/United Kingdom -- England -- Nature. 2012 Nov 15;491(7424):399-405. doi: 10.1038/nature11547. Epub 2012 Oct 24.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Kinghorn Cancer Centre, 370 Victoria Street, Darlinghurst, Sydney, New South Wales 2010, Australia.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23103869" target="_blank"〉PubMed〈/a〉

Description: Intracranial germ cell tumours (IGCTs) are a group of rare heterogeneous brain tumours that are clinically and histologically similar to the more common gonadal GCTs. IGCTs show great variation in their geographical and gender distribution, histological composition and treatment outcomes. The incidence of IGCTs is historically five- to eightfold greater in Japan and other East Asian countries than in Western countries, with peak incidence near the time of puberty. About half of the tumours are located in the pineal region. The male-to-female incidence ratio is approximately 3-4:1 overall, but is even higher for tumours located in the pineal region. Owing to the scarcity of tumour specimens available for research, little is currently known about this rare disease. Here we report the analysis of 62 cases by next-generation sequencing, single nucleotide polymorphism array and expression array. We find the KIT/RAS signalling pathway frequently mutated in more than 50% of IGCTs, including novel recurrent somatic mutations in KIT, its downstream mediators KRAS and NRAS, and its negative regulator CBL. Novel somatic alterations in the AKT/mTOR pathway included copy number gains of the AKT1 locus at 14q32.33 in 19% of patients, with corresponding upregulation of AKT1 expression. We identified loss-of-function mutations in BCORL1, a transcriptional co-repressor and tumour suppressor. We report significant enrichment of novel and rare germline variants in JMJD1C, which codes for a histone demethylase and is a coactivator of the androgen receptor, among Japanese IGCT patients. This study establishes a molecular foundation for understanding the biology of IGCTs and suggests potentially promising therapeutic strategies focusing on the inhibition of KIT/RAS activation and the AKT1/mTOR pathway.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4532372/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4532372/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wang, Linghua -- Yamaguchi, Shigeru -- Burstein, Matthew D -- Terashima, Keita -- Chang, Kyle -- Ng, Ho-Keung -- Nakamura, Hideo -- He, Zongxiao -- Doddapaneni, Harshavardhan -- Lewis, Lora -- Wang, Mark -- Suzuki, Tomonari -- Nishikawa, Ryo -- Natsume, Atsushi -- Terasaka, Shunsuke -- Dauser, Robert -- Whitehead, William -- Adekunle, Adesina -- Sun, Jiayi -- Qiao, Yi -- Marth, Gabor -- Muzny, Donna M -- Gibbs, Richard A -- Leal, Suzanne M -- Wheeler, David A -- Lau, Ching C -- 5T15 LM07093-18/LM/NLM NIH HHS/ -- 5T15 LM07093-19/LM/NLM NIH HHS/ -- 5U54HG003273/HG/NHGRI NIH HHS/ -- U54 HG003273/HG/NHGRI NIH HHS/ -- England -- Nature. 2014 Jul 10;511(7508):241-5. doi: 10.1038/nature13296. Epub 2014 Jun 4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030, USA. ; Texas Children's Cancer and Hematology Centers, Baylor College of Medicine, Houston, Texas 77030, USA. ; 1] Structural and Computational Biology and Molecular Biophysics Program, Baylor College of Medicine, Houston, Texas 77030, USA [2] Medical Scientist Training Program, Baylor College of Medicine, Houston, Texas 77030, USA. ; 1] Texas Children's Cancer and Hematology Centers, Baylor College of Medicine, Houston, Texas 77030, USA [2] National Center for Child Health and Development, Tokyo, 157-8535, Japan. ; Department of Anatomical and Cellular Pathology, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong. ; Department of Neurosurgery, Kumamoto University, Kumamoto, 860-0862, Japan. ; Center for Statistical Genetics, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA. ; Department of Neurosurgery, Saitama Medical University, Saitama, 350-0495, Japan. ; Department of Neurosurgery, Nagoya University, Nagoya, 466-8550, Japan. ; Department of Neurosurgery, Hokkaido University, Hokkaido Prefecture, 060-0808, Japan. ; Department of Neurosurgery, Baylor College of Medicine, Houston, Texas 77030, USA. ; Department of Pathology, Baylor College of Medicine, Houston, Texas 77030, USA. ; Medical Scientist Training Program, Baylor College of Medicine, Houston, Texas 77030, USA. ; Department of Biology, Boston College, Chestnut Hill, Maryland 02467, USA. ; 1] Texas Children's Cancer and Hematology Centers, Baylor College of Medicine, Houston, Texas 77030, USA [2] Medical Scientist Training Program, Baylor College of Medicine, Houston, Texas 77030, USA [3] Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas 77030, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24896186" target="_blank"〉PubMed〈/a〉